Recyclable polymer- and silica-supported Ruthenium(II)-Salen bis-pyridine catalysts for the asymmetric cyclopropanation of olefins

Article abstract of DOI:10.1002/adsc.200800779

Homogeneous ruthenium(II)-salen bis-pyridine complexes are known to be highly active and selective catalysts for the asymmetric cyclopropanation of terminal olefins. Here, new methods of heterogenization of these Ru-salen catalysts on polymer and porous silica supports are demonstrated for the facile recovery and recycle of these expensive catalysts. Activities, selectivities, and recyclabilities are investigated and compared to the analogous homogeneous and other supported catalysts for asymmetric cyclopropanation reactions. The catalysts are characterized with a variety of methods including solid state cross-polarization magic-angle spinning (CP MAS) ¹³C and ²⁹Si NMR, FT-IR, elemental analysis, and thermogravimetric analysis. Initial investigations produced catalysts possessing high selectivities but decreasing activities upon reuse. Addition of excess pyridine during the washing steps between cycles was observed to maintain high catalytic activities over multiple cycles with no impact on selectivity. Polymer-supported catalysts showed superior activity and selectivity compared to the porous silicasupported catalyst. Additionally, a longer, flexible linker between the Ru-salen catalyst and support was observed to increase enantioselectivity and diastereoselectivity, but had no effect on activity of the resin catalysts. Furthermore, the polymer-supported Ru-salen-Py₂ catalysts were found to generate superior selectivities and yields compared to other leading heterogeneous asymmetric cyclopropanation catalysts.

Full text of DOI:10.1002/adsc.200800779

FULL PAPERS
DOI: 10.1002/adsc.200800779
Recyclable Polymer- and Silica-Supported Ruthenium(II)-Salen
Bis-pyridine Catalysts for the Asymmetric Cyclopropanation of
Olefins
Christopher S. Gill,a Krishnan Venkatasubbaiah,a and Christopher W. Jonesa,b,*
a
School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive NW, Atlanta, Georgia
30332, USA
Fax : (+1)-404-894-2866; phone: (+1)-404-385-1683; e-mail: cjones@chbe.gatech.edu
School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Dr., Atlanta, Georgia 30332, USA
b
Received: December 16, 2008; Revised: April 8, 2009; Published online: June 3, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800799.
Abstract: Homogeneous ruthenium(II)-salen bis-pyr- cycles was observed to maintain high catalytic activi-
idine complexes are known to be highly active and ties over multiple cycles with no impact on selectivi-
selective catalysts for the asymmetric cyclopropana- ty. Polymer-supported catalysts showed superior ac-
tion of terminal olefins. Here, new methods of heter- tivity and selectivity compared to the porous silica-
ogenization of these Ru-salen catalysts on polymer supported catalyst. Additionally, a longer, flexible
and porous silica supports are demonstrated for the linker between the Ru-salen catalyst and support
facile recovery and recycle of these expensive cata- was observed to increase enantioselectivity and dia-
lysts. Activities, selectivities, and recyclabilities are stereoselectivity, but had no effect on activity of the
investigated and compared to the analogous homo- resin catalysts. Furthermore, the polymer-supported
geneous and other supported catalysts for asymmet- Ru-salen-Py2 catalysts were found to generate supe-
ric cyclopropanation reactions. The catalysts are rior selectivities and yields compared to other lead-
characterized with a variety of methods including ing heterogeneous asymmetric cyclopropanation cat-
solid state cross-polarization magic-angle spinning alysts.
(CP MAS) 13C and 29Si NMR, FT-IR, elemental anal-
ysis, and thermogravimetric analysis. Initial investiga-
tions produced catalysts possessing high selectivities Keywords: asymmetric cyclopropanation; enantiose-
but decreasing activities upon reuse. Addition of lectivity; heterogeneous catalysis; ruthenium-salen;
excess pyridine during the washing steps between supported catalysts
Introduction
have been shown to demonstrate high activities and
selectivities for the cyclopropanation of olefins
Asymmetric synthesis of chiral cyclopropyl chemicals (Scheme 1), while maintaining functional group toler-
is of particular importance in the pharmaceutical and ance for a range of electronically diverse olefins.[3,4]
agro-chemical industries as an alternative method of
With advancements in homogeneous asymmetric
procuring these important chiral building blocks used cyclopropanation catalysis, several researchers have
in the preparation of drugs and pesticides.[1] Research- been working on the development of supported,
ers have developed numerous homogeneous catalysts single-sited heterogeneous catalysts in parallel. Immo-
to facilitate synthesis of these chiral cyclopropyl prod- bilization of these catalysts on solid phase supports
ucts.[2] Optimizing catalysts to produce desired prod- allows for the facile recovery and reuse of the asym-
ucts in high atom economy has been of particular im- metric catalyst, which can be important for a variety
portance. Consequently, all asymmetric cyclopropana- of economic, environmental, and quality control rea-
tion catalysts are judged based on their activity, dia- sons. Research in this area has mainly focused on sup-
steroselectivity to cis or trans cyclopropyl products, ported copper, rhodium, and ruthenium complexes.[5,6]
and enantioselectivities (ee) of the resulting cis and While much research has focused on supported
trans products. Recently, ruthenium-salen catalysts copper bis(oxazoline) (Box) and related complexes,[6]
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Recyclable Polymer- and Silica-Supported Ruthenium(II)-Salen Bis-pyridine Catalysts
FULL PAPERS
Scheme 1. Ru(II)-salen bis-pyridine-catalyzed asymmetric cyclopropanation of styrene with ethyl diazoacetate.
increasing reports of supported ruthenium catalysts vimetric analysis. This report highlights the synthesis
have appeared due to their high activity, selectivity, and characterization of these immobilized catalysts, as
and the advantages of ruthenium over the copper- well as investigations into their activity, selectivity,
based systems: superior diastereoselectivities, func- and recyclability in the cyclopropanation of styrene
tional group tolerance, and ease of use. These reports and other terminal olefins. Additionally, these poly-
include ruthenium pyridine-bis(oxazoline) (PyBox) mer supported Ru-salen-Py2 catalysts generated supe-
complexes grafted to polymers,[7,8] encapsulated rior yields and selectivities compared to other leading
within polymers,[9] and grafted to silica.[10] Additional solid-supported asymmetric cyclopropanation cata-
examples of polymer-[11] and silica-supported[12] ruthe- lysts.
nium porphyrins exist. Despite the promising results
of homogeneous Ru-salen cyclopropanation catalysts,
no reports of Ru-salen catalysts covalently grafted to Results and Discussion
solid supports exist at present. Only a single report of
Ru-salen catalysts coordinated to poly(4-vinylpyri- Ruthenium(II)-Salen Bis-Pyridine Polymer Resin
dine) for aldehyde olefination has appeared, but this Catalysts (4a, 4b): Synthesis and Characterization
catalyst was hampered by poor recyclability due to
leaching of the active Ru-salen catalyst by dissocia- Borrowing from previous work developed in our re-
À
tion of the Ru N coordination to the polymer sup- search group, styrene-modified mono-functionalized,
port,[13] thus highlighting the need for covalent immo- unsymmetrical, chiral salen monomers (2a, 2b) were
bilization to solid supports.
synthesized.[15,17–19] These styrene-modified salen com-
Building on past work in our research group fo- pounds were utilized in the synthesis of polymer- and
cused on development of supported Co-salen cata- silica-supported materials. Mono-functionalized, un-
lysts,[14–17] alternative techniques are developed here symmetric salen ligands were preferred (in compari-
to provide the first report of heterogenized Ru-salen son to bi-functionalized, symmetric, bis-styryl modi-
complexes covalently grafted to solid supports. The fied salen ligands[20]) due to the greater degree of flex-
goal of this work was to develop a solid catalyst, ibility and increased distance from the polymer sup-
stable over multiple cycles, that retained the high ac- port imparted on the pendant catalyst site. In the pro-
tivity, diastereoselectivity, and enantioselectivities ex- posed bimetallic transition state of the Co-salen-
hibited by the homogeneous analogue in the asym- catalyzed hydrolytic kinetic resolution (HKR) mecha-
metric cyclopropanation of olefins with ethyl diazo- nism, this flexibility greatly affected the catalyst per-
ACHTUNGTRENNUNG
acetate (EDA). This was accomplished via the immo- formance.[14,21] In the monometallic mechanism of the
bilization of monofunctionalized, unsymmetrical, Ru-salen cyclopropanation reaction, this flexibility
chiral salen ligands on polymer and silica supports to could be less important. However, the linker does
eventually produce covalently bound, surface-grafted impact the steric hindrance of the polymer backbone
Ru(II)-salen bis-pyridine catalysts. These catalysts near the catalytically active site, which can be impor-
were characterized via solid state CP MAS 13C and tant for polymer-supported catalysts in general. In-
29Si NMR, FT-IR, elemental analysis, and thermogra- soluble, cross-linked, salen-functionalized polymer
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Christopher S. Gill et al.
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À
À
À
À
À À
Scheme 2. Synthesis of polymer resin-supported Ru(II)-salen bis-pyridine catalysts [a: R= C6H4 , b: R= C6H4 CH2
À À
O
À
ACHTUNGTRENNUNG(CH2)2 O CH2 ].
resins (3a, 3b) were synthesized in high yield by reac-
tion of the styryl-salen monomers with divinylbenzene
(Scheme 2). Ruthenium(II)-salen bis-pyridine poly-
mer resin catalysts (4a, 4b) were then synthesized fol-
lowing modified published procedures[3] by initial
treatment with n-butyllithium to deprotonate the phe-
nolic protons of the salen ligand, followed by metalla-
tion with dichloroACHTNUGRTENUNG(p-cymene)ruthenium(II) dimer in
the presence of excess pyridine. Elemental analysis in-
dicated a ruthenium loading of 0.34 mmol/g at a 6.2:1
N:Ru ratio and 48% metallation efficiency for 4a, and
0.37 mmol/g ruthenium at a 5.7:1 N:Ru ratio and
53.5% metallation efficiency for 4b. Moderate metal-
lation efficiencies are common when working with
solid supports and likely resulted from reacting stoi-
chiometric equivalents of n-butyllithium (2:1) and
ruthenium dimer (0.5:1) to the solid-supported salen.
This metallation procedure was sufficient for small
molecule Ru-salen complexes,[3] but was likely hin-
Figure 1. FT-IR spectra of (a) non-metallated H2salen poly-
mer resin 3b and (b) metallated Ru(II)-salen-Py2 polymer
resin 4b.
dered by transport issues with the support. Extended Upon complexation, this band shifted towards higher
reaction times at ambient temperature were utilized frequencies at 1322 cmÀ1. Additionally, the nRu and
À
O
to maximize the metallation efficiency.
nRu bands appeared at 539 and 470 cmÀ1, respective-
À
N
The successful formation of the Ru(II)-salen-Py2 ly in 4b.[24] These frequency shifts and new bands sup-
complex was evidenced by FT-IR analysis (Figure 1). port coordination of ruthenium to the nitrogen and
The characteristic imine stretch appeared at oxygen of the salen ligand and formation of the
1628 cmÀ1 for 3b. Upon complexation with ruthenium, Ru(II)-salen-Py2 complex.
there was a sharp decrease in intensity of this band as
it shifted towards lower frequencies at 1600 cmÀ1, re-
sulting from a shift of electron density from the imine SBA-15-Supported Ru-Salen Catalyst (8): Synthesis
towards ruthenium.[22] Additional support for the for- and Characterization
mation of the Ru-salen complex was seen in the shift
of the carbon-oxygen stretch of the phenolic oxygen. Ruthenium-salen bis-pyridine catalyst was also graft-
The non-metallated complex displayed a moderate ed to the surface of SBA-15 mesoporous silica
peak at 1270 cmÀ1, characteristic of the nCÀ stretch.[23] (Scheme 3). A trimethoxysilane-modified, chiral salen
O
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Recyclable Polymer- and Silica-Supported Ruthenium(II)-Salen Bis-pyridine Catalysts
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5 was synthesized via thiol coupling of mercaptopro-
pyltrimethoxysilane (MPTMS) with styryl-salen 2a at
46% isolated yield.[14,25] Compound 5 was immobilized
on 60 ꢁ mesoporous SBA-15 silica by condensation
with surface hydroxy groups forming material 6. Un-
reacted silanol groups were capped with hexamethyl-
disilazane (HMDS) to form material 7 prior to the
metallation procedure with n-butyllithium and ruthe-
nium dimer. Thermogravimetric analysis (TGA) indi-
cated an organic content of 5.0% and 6.3% for 6 and
7, respectively. These data equated to a loading of
0.075 mmol salen/g dry silica for 6. Elemental analysis
of 8 indicated a ruthenium loading of 0.031 mmol/g
and a N:Ru ratio of 6.2, equating to a 48% metalla-
tion efficiency. This moderate metallation efficiency
was, again, likely a result of using a stoichiometric
amount of n-butyllithium and ruthenium dimer in
combination with the solid support.
Grafting of salen species on the silica surface was
supported by cross-polarization magic-angle spinning
(CP MAS) 13C and 29Si NMR spectra for material 7
(see Supporting Information). Carbon resonances ap-
À
peared in the aliphatic region d=20–50 ppm (Si CH2,
À
À
CMe3, CH2, cyclohexyl CH2, cyclohexyl-CH, S CH2,
À
Ph CH2), aromatic region d=120–140 ppm, and
imine region d=160 ppm (C=N). In addition to
framework silicon Q2, Q3, and Q4 resonances (d=À94
to À116 ppm), resonances corresponding to condensa-
tion of one to three methoxy groups of compound 5
(d=À45 to À57 ppm) appeared in the 29Si NMR spec-
trum. The presence of trimethylsilyl capping groups in
material 7 was evidenced by the sharp peaks centered
at d=0.7 ppm [(CH3)3Si] in the 13C NMR spectrum
and d=13 ppm (Me3Si O) in the 29Si NMR spectrum.
À
FT-IR analysis confirmed the presence of organic
species in 6–8 by the appearance of aliphatic nCÀ
H
stretch at 2967 cmÀ1 and imine nC stretch centered
=
N
at 1635 cmÀ1 (Figure 2). As expected, the strongest
peak in the FT-IR spectra for materials 6–8 corre-
sponded to the nSiÀ stretch from 1000–1280 cmÀ1 re-
O
sulting from the SBA-15 silica support. A strong nOÀ
H
stretch appeared in material 6 from 3200 to 3700 cmÀ1
confirming the presence of surface silanol groups and
the inability to react all silanols with bulky compound
5. This peak diminished but did not disappear in ma-
terial 7 after the capping step with HMDS possibly
due to inaccessible, uncapped silanols and/or the phe-
nolic hydroxy groups in the salen ligand. In conjunc-
tion, a sharp peak appeared at 850 cmÀ1, correspond-
ing to the nSiÀ stretch in the trimethylsilyl capping
C
groups. Upon metallation with ruthenium, no nOÀ
H
stretch was observed indicating formation of the
ruthenium-salen complex.
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Christopher S. Gill et al.
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ee, 91% cis ee, entry 5) compared to 4a (8.8 trans/cis
ratio, 87% trans ee, 77% cis ee, entry 2), slightly less
than that of the homogeneous catalyst (entry 1). Re-
lated work using polymer brush-supported Co-salen
catalysts for the HKR of epoxides demonstrated a
dramatic difference in activity between the rigid
styryl and flexible ethylene glycyl linkers.[17] However,
this observation was likely a consequence of the bi-
metallic mechanism of Co-salen-catalyzed HKR. The
Ru-salen-catalyzed cyclopropanation of olefins fol-
lows a monometallic mechanism, and therefore, the
length/flexibility of the linker should not have as sig-
nificant an impact on the rates. This seems to be the
case, as catalysts 4a and 4b appear to be equally
active.[26]
SBA-15-supported catalyst 8 required longer reac-
tion times to reach high yields than the polymer resin
catalysts, but similar selectivities were achieved (9.8
trans/cis ratio, 89% trans ee, 80% cis ee, entry 8). Un-
fortunately, ees were only slightly better than those
resulting from catalyst 4a and less than those of 4b.
Figure 2. FT-IR spectra of (a) SBA-H2salen 6, (b) SBA-
H2salen capped 7, and (c) SBA-Ru-salen-Py2 capped 8.
Catalytic Results and Discussion
All cyclopropanation reactions were evaluated in The decreased selectivities for 8 may have resulted
terms of yields, diastereoselectivities (trans/cis product from steric hindrance with the silica surface. How-
ratio), and enantioselectivities (Table 1). Initial reac-
ACHTUNGTRENeNUNG ver, a more likely explanation may result from the
tions using catalysts 4a, 4b, and 8 appeared promising nature of the silica support itself. In the case of the
(Table 1, entries 2, 5, 8). Yields were similar (ꢀ95%), SBA-15-supported catalyst, it proved impossible to
but selectivities of these catalysts suffered slightly in react all silanol groups in bare SBA-15 with excess
comparison to the homogeneous Ru-salen reported methoxysilane-modified salen 5 due to the bulky
previously.[3] Formation of dimeric side products di- nature of the compound. Consequently, all remaining
ethyl maleate and diethyl fumarate was not detected accessible silanol groups were capped to form materi-
via GC when using styrene as the olefin reactant. The al 6 prior to the metallation procedure to prevent re-
polymer resin catalysts appeared more active than the action with n-butyllithium and subsequent immobili-
silica-based catalyst by reaching ꢀ95% yield in five zation of surface bound, non-chiral, ruthenium spe-
hours versus 24 hours. Catalyst 4b achieved higher se- cies. If any of the silanols present in the mesopores of
lectivities in all areas (10.6 trans/cis ratio, 94% trans SBA-15 survived the capping step (or if there are
Table 1. Results summary for the cyclopropanation of styrene with various catalysts.[a]
Entry Catalyst Mol%
catalyst
Solvent Cycle number Time [h] Yield [%][b] trans/cis ratio trans ee [%][c,d] cis ee [%][d,e]
1
2
3
4
5
6
7
8
1[3]
4a
4a
4a
4b
4b
4b
8
1
2
2
2
2
2
2
2
2
2
2
DCM
DCM
DCM
THF
DCM
DCM
DCM
DCM
DCM
THF
1
1
2
1
1
2
3
1
2
1
2
3
4
8
4
5
8
11
24
74
24
24
95
95
80
91
99
94
93
95
49
79
17
10.8
8.8
8.9
10.4
10.6
10.9
9.1
9.8
7.7
12.1
10.0
99
87
88
84
94
95
95
89
80
79
77
96
77
80
73
91
92
91
80
56
67
62
9
10
11
8
8
8
THF
[a]
Initial reactions performed using 0.5 mmol EDA, 2.5 mmol styrene, 3.5 mL solvent, and 0.5 mmol tridecane (internal
standard) at room temperature inside a glove box.
Determined via GC calibration.
Enantioselectivity towards the (1R,2R) product.
Determined via chiral GC.
[b]
[c]
[d]
[e]
Enantioselectivity towards the (1R,2S) product.
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Recyclable Polymer- and Silica-Supported Ruthenium(II)-Salen Bis-pyridine Catalysts
FULL PAPERS
yields at long times, as is commonly done in the litera-
ture. Reporting single point yields at long times can
be misleading, as this practice can mask the true ki-
netics, activity, recyclability, and deactivation. The
yields reported in this paper are not collected at long
times. Instead kinetics were collected for most reac-
tions and yields are reported at the corresponding
times. Figure 3 displays representative data for the de-
activation of polymer resin catalyst 4b. An analogous
figure for catalyst 4a appears in the Supporting Infor-
mation. Using kinetic data, instead of single point
yields, a clearer picture of catalyst deactivation can be
observed between the first and third cycle for catalyst
4b.
Catalyst deactivation proved to be an initial hurdle
during this work. However, it was observed this could
be minimized by the addition of pyridine during the
washing steps between cycles. Addition of pyridine to
each washing step proved to have a positive effect on
catalyst stability over several cycles as seen by over-
Figure 3. Yield of cyclopropyl products versus time using
~
^
catalyst 4b: (&) first cycle, ( ) third cycle, and ( ) third
cycle with pyridine treatment between all previous cycles.
many oxygens associated with siloxane bridges acces- lapping kinetics between the first cycle and third
sible to the metal center), then they could create ad- cycle with pyridine treatment (Figure 3). As a result,
verse interactions with the Ru-salen catalyst, poten- all recycle experiments were repeated using the pyri-
tially explaining the decreased ees, as seen experimen- dine treatment between cycles (Table 2). At slightly
tally.
longer times (6 h), very high yields (ꢀ97%) could be
It should be noted that extensive studies were per- achieved for both polymer resin catalysts over the
formed trying to replicate previous metallation proce- three cycles tested without any apparent deactivation
dures[27] that used triethylamine instead of a stronger (Table 2, entries 1–6). Initial cycles gave similar re-
deprotonating agents such lithium diisopropylamide sults as shown in Table 1, and subsequent cycles
used previously[3] or n-butyllithium in this work. How- showed marginally better selectivities (entries 1–2, 4–
ever, the proposed Ru-salen could never be isolated 5). This marginal increase may result from removal of
using homogeneous or heterogeneous salens under a any residual, non-chiral ruthenium species that may
variety of conditions. For example, when metallating not have been removed during the filtration steps fol-
the supported salens in this way, filtration with DCM lowing the metallation procedure. Catalysts 4a and 4b
always removed the brownish/red color associated displayed very consistent yields and selectivities over
with the ruthenium, resulting in no color change to three cycles, with catalyst 4b approaching the perfor-
the parent material. In both cases, no active cyclopro- mance of the homogeneous Ru-salen except for over-
panation catalyst was ever isolated. For this reason, all activity (entry 5).
the stronger deprotonating agent was used.
The addition of excess pyridine during the washing
Recycle studies using catalysts 4a, 4b, and 8 dis- steps is thought to stabilize the ruthenium center
played very similar diastereoselectivities and enantio- during the washing procedure. The Ru(II)-salen bis-
selectivities as the initial runs, but decreased rates pyridine complex must dissociate a pyridine ligand
were observed, leading to longer reaction times prior to entering the catalytic cycle. This vacant coor-
(Table 1, entries 3, 6, 7, 9). Catalyst 4b required over dination site permits formation of the ruthenium car-
twice as long to reach 95% yield in the third run (11 bene intermediate prior to carbene addition across
h) versus the first run (5 h) (Figure 3). These data the carbon-carbon double bond of the olefin. After
may suggest a fractional loss of active Ru-salen spe- complete consumption of the EDA and ruthenium
cies with each successive cycle, possibly due to leach- carbene by excess styrene, a vacant coordination site
ing of ruthenium during the washing steps between remains on the ruthenium center. Addition of excess
cycles or catalyst poisoning. Studies using THF as a pyridine shifts the equilibrium towards binding two
solvent instead of DCM resulted in lower yields and pyridine ligands, thus stabilizing the Ru-salen com-
ees but curiously higher diastereoselectivities (en- plex, and inhibiting leaching of ruthenium metal from
tries 4 and 10). Recycle studies using THF solvent dis- the ligand. Elemental analysis data indicated that pyr-
played similar losses in catalytic activity as using idine washing did affect the ruthenium content in the
DCM (entry 11).
recycled catalysts. Compared to the fresh catalyst 4a,
To fully understand the catalytic activities, kinetic the used catalyst after three cycles using the pyridine
data were collected rather than analyzing single point treatment retained 85% of the initial ruthenium con-
Adv. Synth. Catal. 2009, 351, 1344 – 1354
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Christopher S. Gill et al.
Table 2. Results summary for the cyclopropanation of styrene with various catalysts by modified recycling method.[a]
FULL PAPERS
Entry Catalyst Mol%
catalyst
Solvent Cycle number Time [h] Yield [%][b] trans/cis ratio trans ee [%][c,d] cis ee [%][d,e]
1
2
3
4
5
6
7
8
4a
4a
4a
4b
4b
4b
8
8
8
8
8
2
2
2
2
2
2
1
1
1
1
1
1
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
THF
1
2
3
1
2
3
1
2
3
1
2
3
6
6
6
6
6
6
24
24
48
24
24
48
97
97
99
97
99
99
27
20
15
18
15
11
9.1
9.4
8.9
10.7
10.9
10.6
7.5
7.7
6.3
90
93
91
94
96
96
81
85
80
73
75
69
82
88
86
90
95
93
56
50
35
42
45
32
9
10
11
12
8.0
7.0
5.2
THF
THF
8
[a]
Initial reactions performed using 0.5 mmol EDA, 2.5 mmol styrene, 3.5 mL solvent, and 0.5 mmol tridecane (internal
standard) at room temperature inside a glove box.
Determined via GC calibration.
Enantioselectivity towards the (1R,2R) product.
Determined via chiral GC.
[b]
[c]
[d]
[e]
Enantioselectivity towards the (1R,2S) product.
Table 3. Elemental analysis comparison between fresh and recycled catalyst 4a.
Catalyst
% Ru
% N
Ru loading [mmolg]À1
Relative Ru content
N/Ru mol ratio
Fresh
3rd Cycle (with Py)
3rd Cycle (No Py)
3.4%
2.9%
2.5%
2.9%
2.8%
2.7%
0.34
0.29
0.24
100%
85%
72%
6.2
7.0
7.8
tent (Table 3). Without the addition of pyridine, the son to the polymer resin-supported catalysts, indicat-
ruthenium content dropped to 72% of the fresh cata- ing such a sensitive catalyst may be more difficult to
lyst. Furthermore, the nitrogen to ruthenium mol immobilize on silicas or other inorganic oxides, where
ratio increased from an initial value of 6.2 (indicating potentially deleterious interactions with surface hy-
an incomplete metallation procedure, since an Ru- droxy groups or siloxane bridges may be present. This
salen-Py2 complex should have N/Ru=4) for the result appears in agreement with siliceous mesocellu-
fresh catalyst to 7.0 and 7.8 for the recycled catalysts lar foam (MCF)-supported Cu-Box and Cu-PyBox in-
with and without the pyridine treatments, respective- vestigations in which the authors suggest capping of
ly.
surface hydroxy groups was paramount to the activity
Attempts to assess changes to the Ru-salen cata- and stability of the cyclopropanation catalyst.[29] More
lysts upon recycling via FT-IR analysis proved incon- detailed studies of the silica-supported Ru-salen
clusive owing to overlapping peaks from pyridine system are needed.
(1633 and 1598 cmÀ1) and the imine peaks of interest
The Ru-salen polymer resin catalysts (4a, 4b) com-
(1631 and 1607 cmÀ1, see Supporting Information).[13] pare extremely favorably against the best supported
No apparent differences between the fresh and spent copper bis(oxazoline) catalysts to date.[6] While the
catalysts were observed in the nCÀ stretching region supported Ru-salen and Cu-Box catalysts exhibit
O
(commonly 1275 cmÀ1 for non-metallated and comparable activities and enantioselectivities (gener-
1310 cmÀ1 for the metallated ruthenium Schiff base ally >90%), Ru-salen catalysts exhibit extremely high
complexes).[22–24,28] In addition, the nRu and nRu
yields and are about four times more diastereoselec-
À
À
O
N
stretches (450 cmÀ1 and 530 cmÀ1, respectively) were tive to the trans products (trans/cis=9–11) than the
only minutely visible, due to the low ruthenium load- Cu-Box systems (generally trans/cis=2–3).[30] Addi-
ings on the solid supports compared to analogous tionally, use of Ru-salen catalysts requires no activa-
studies of homogeneous small molecule complexes.
tion step, unlike the Cu-Box systems, which require
Catalyst 8 showed less consistent results over three addition of phenylhydrazine prior to reaction. Sup-
cycles and its selectivities were moderate in compari- ported Ru-salen catalysts also supercede Ru-porphy-
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Recyclable Polymer- and Silica-Supported Ruthenium(II)-Salen Bis-pyridine Catalysts
FULL PAPERS
Table 4. Summary of results for the cyclopropanation of various terminal olefins with catalyst 4b.[a]
Entry Olefin
Solvent Time [h] Conversion [%] Yield [%][b] trans/cis ratio trans ee [%][c,d] cis ee [%][d,e]
1
2
3
4
5
6
Pentene
EVE
EVE
MMA
Piperylene DCM
Styrene DCM
DCM
Neat
DCM
DCM
39
24
48
52
48
6
93
75
85
100
100
100
5.0
7.5
13
36
48
97
2.7
2.1
2.3
10.1
1.6
54
36
50
34
33
80
À7.5
À26
55
55
10.7
94
90
[a]
Reactions performed using 0.25 mmol EDA, 1.25 mmol olefin, 1.75 mL solvent, and 0.25 mmol tridecane (internal stan-
dard) at room temperature inside a glove box.
Determined via GC calibration.
Enantioselectivity towards the (1R,2R) product.
Determined via chiral GC.
[b]
[c]
[d]
[e]
Enantioselectivity towards the (1R,2S) product.
rin[11] and Ru-PyBox[7] catalysts in terms of yields and of the olefins studied, with moderate enantioselectivi-
enantioselectivities, but are comparable in diastereo- ties and low diastereoselectivity (Table 4, entry 5).
selectivity.
After successful cyclopropanation studies using sty-
rene, the utility of supported Ru-salen catalysts on a Conclusions
range of electronically diverse terminal olefins was in-
vestigated. These studies examined the most active This work demonstrates the first report of covalently
and selective catalyst 4b at 2 mol% catalyst (Table 4). grafted Ru-salen complexes on solid supports. These
Generally, the more activated olefins resulted in catalysts were observed to be highly active, selective,
higher yields of cyclopropanated products. The differ- and recyclable for use in the asymmetric cyclopropa-
ences between the product yields and ethyl diazoace- nation of olefins useful in the pharmaceutical and
tate (EDA) conversions resulted from formation of agro-chemical industries. Two polymer resin- and one
dimeric side products diethyl maleate and diethyl fu- SBA-15-supported Ru(II)-salen bis-pyridine catalyst
marate and minor amounts of trimer side product, were synthesized and tested in the cyclopropanation
presumably triethyl cyclopropane-1,2,3-tricarboxylate. of styrene. All three generated the desired products
Cyclopropanation of pentene resulted in very low in high yield and trans selectivity with moderate to
yields (5%) of product at moderate enantioselectivity. high enantioselectivities. Polymer resin catalyst 4b
Improved yields and selectivities of products were ob- was observed to generate products with the highest
served using ethyl vinyl ether (EVE). In contrast to selectivities and yield, an observation potentially oc-
studies using the homogeneous catalyst, the use of curring from lessened steric hindrance due to the
solvent instead of neat olefin resulted in significant lengthened linker between the Ru-salen active site
improvements to the ees and moderate increases in and polymer support. Fractional losses in activity
yield and diastereoselectivity. This difference likely were observed upon recycle of these catalysts while
resulted from positive solvent swelling effects of product selectivities were unchanged. However, addi-
DCM on the polymer resin, reducing steric hindrance tion of pyridine during the washing steps between
near the active site. The homogeneous Ru-salen cata- cycles was observed to retain the high activities of the
lyst would not experience these issues, explaining why polymer resin catalysts after three cycles by stabilizing
no difference was observed between neat and solvat- the complex between cycles and decreasing leaching
ed reactions.[3] As a result of this observation, all stud- of ruthenium. Moderate enantioselectivities were ob-
ies using different olefins were performed using sol- served using the SBA-15-supported catalyst 8, possi-
vent. Contrary to the case with homogeneous Ru- bly due to adverse reactions with the silica surface.
salen where very minimal cis products were observed Additional studies with other terminal olefins demon-
(100 trans/cis ratio),[3] appreciable amounts of cis strated better catalyst performance for the more acti-
products from the cyclopropanation of methyl metha- vated olefins, consistent with previous reports. In con-
crylate (MMA) were observed using catalyst 4b (10.1 trast to the homogeneous case, the use of solvent re-
trans/cis ratio). Consistently, a reversal in enantiose- sulted in increased yields and selectivities, presumably
lectivity of the MMA cyclopropanation products was by making the active site more accessible and less
observed using chiral GC, showing 7.5% trans ee hindered inside the swollen polymer resin. These
(1S,2S) and 26% cis ee (1S,2R). Cyclopropanation of solid-supported analogues of homogeneous Ru-salen
trans piperylene generated the highest product yields catalysts show promise in the facile recycling of these
Adv. Synth. Catal. 2009, 351, 1344 – 1354
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Christopher S. Gill et al.
FULL PAPERS
expensive catalysts for repeated processes. Addition- Synthesis of Insoluble Polymer Resin-Supported
ally, polymer resin-supported Ru-salen catalysts 4a Ru(II)-Salen Bis-pyridine Catalysts (4a) and (4b)
and 4b generated superior selectivities and yields
An insoluble polymer resin was synthesized by combining
versus other leading solid-supported, asymmetric cy-
divinylbenzene (521 mg, 4 mmol, inhibitors removed and
freshly dried), styryl-salen[15,17,19] (593 mg for 4a, 681 mg for
4b, 1 mmol), and AIBN (44 mg, 0.27 mmol) in chloroben-
zene (2.2 g). The reaction mixture was stirred under argon
(808C, 48 h). The solid polymer resin was recovered via fil-
tration and washed with copious methanol, hexane, DCM,
THF, and ether. The resin was ground to a powder with a
mortar and pestle, filtered again, and dried under high
vacuum (room temperature, 12 h). The salen polymer resin
was then metallated with ruthenium using a slightly modi-
fied procedure from the literature.[3] Inside a glove box, n-
butyllithium (1.6M in hexane, 170 mg, 0.4 mmol) was added
to a mixture of polymer resin (containing 0.2 mmol of salen)
and THF (1.44 g) cooled to À238C. The mixture was stirred
and allowed to warm to room temperature (6 h). A mixture
of [Ru(Cy)2Cl2]2 (61 mg, 0.1 mmol), THF (2.1 g), and pyri-
dine (127 mg, 1.6 mmol) was added to the lithiated polymer
mixture and stirred at room temperature inside the glove
box (48 h). The metallated Ru-salen polymer resin was re-
covered via filtration and washed with copious THF, metha-
nol, DCM, toluene, hexane, and ether. The resulting dark
brown solid was dried under high vacuum at room tempera-
ture overnight and stored in the glove box.
clopropanation catalysts.
Experimental Section
General Remarks
All chemicals were purified prior to use and stored in a ni-
trogen glove box, and all reactions were initiated in the
glove box. Dichloromethane (DCM) was distilled over calci-
um hydride. Tetrahydrofuran (THF) and toluene were dis-
tilled over sodium. Hexane (<50 ppm water) was further
dried over columns of activated copper oxide and alumi-
na.[31] Styrene was washed to remove inhibitors (5% NaOH,
water, and brine), dried over magnesium sulfate, distilled
over calcium hydride, and stored at À238C in the glove box
prior to use. Divinylbenzene was washed to remove inhibi-
tors (5% NaOH, water, and brine) and dried over sodium
sulfate immediately prior to use. Tridecane was dried over
calcium hydride, vacuum distilled, and stored in the glove
box. Ethyl diazoacetate (EDA) was degassed via three
freeze-pump-thaw cycles and stored in the glove box at
À238C.
Instrumentation
Synthesis of SBA-15-Supported Ru(II)-Salen
Bis-pyridine Catalyst (8)
Cross-polarization magic angle spinning (CP-MAS) solid-
state NMR spectra were measured using a Bruker DSX
300 MHz spectrometer. Samples were packed in 7 mm zirco-
nia rotors and spun at 6.6 kHz. Solid state 13C CP-MAS
spectra were recorded using 3000 scans, a 908 pulse length
of 4 ms, and recycle times of 4 s. Solid state 29Si CP-MAS
were recorded using 5000 scans, a 908 pulse length of 5 ms,
and recycle times of 5 s. Conversions of ethyl diazoacetate
(EDA), product yields (via calibration curves from pure
samples), and trans/cis product ratios were calculated using
capillary gas-phase chromatography on a Shimadzu GC
2010 equipped with an FID detector and a SHRX5 column
(15 mꢂ0.25 mmꢂ0.25 mm). The oven profile heated from
508C to 2508C at 108C/min. When using styrene as the
olefin, enantiomeric excesses of the trans cyclopropyl prod-
ucts were measured on a Shimadzu GC 2010 equipped with
an FID detector and a Beta DEX 225 column (30 mꢂ
0.25 mmꢂ0.25 mm). The oven profile heated from 1008C to
1408C at 0.58C/min. cis-Cyclopropyl product ees were mea-
sured on a Shimadzu 14 A GC with an FID detector and an
Astec Chiraldex g-TA column (40 mꢂ0.25 mmꢂ0.12 mm)
using the same oven profile as the trans products. When
using other olefins, similar analytical methods were used as
previously reported.[3] A Netzsch Thermoanalyzer STA 409
was used for thermogravimetric analysis (TGA) and differ-
ential scanning calorimetry (DSC) with a heating rate of
108C/min in air. Elemental analyses were performed by Co-
lumbia Analytics Lab (Tucson, AZ, USA) or Galbraith Lab-
oratories, Inc. (Knoxville, TN, USA).
SBA-15 was synthesized according to published proce-
dures,[32] dried under high vacuum (2508C, 3 h), and stored
in a nitrogen glove box. A silane-modified salen species 5
was synthesized using procedures developed within our re-
search group.[14] The salen was post-grafted to the SBA-15
support by refluxing silane-modified salen 5 (290 mg) and
SBA-15 (1.7 g) in anhydrous toluene (16 g) under argon (24
h). The resulting solid was recovered via filtration and
washed with copious toluene, DCM, hexane, and ether. The
salen-functionalized SBA-15 6 was dried under high vacuum
at room temperature (12 h). Unreacted SBA surface hy-
droxy groups were then capped by stirring salen-functional-
ized SBA-15 6 (500 mg) and hexamethyldisilazane (HMDS,
500 mg) in hexane (10 g) under argon at room temperature
(48 h). The capped salen-modified SBA-15 7 was recovered
via filtration, washed with hexane, toluene, DCM, hexane,
and ether, and dried overnight at room temperature under
high vacuum. The capped, salen-functionalized SBA-15 was
then metallated with ruthenium similar to the procedure de-
scribed above. Inside a glove box, n-butyllithium (1.6M in
hexane, 54 mg, 0.13 mmol) was added to a mixture of
capped, salen-modified SBA-15 7 (494 mg, 0.064 mmol salen
ligand) and THF (460 mg) cooled to À238C. The mixture
was stirred and allowed to warm to room temperature (6 h).
A mixture of [Ru(Cy)2Cl2]2 (20 mg, 0.032 mmol), THF
(690 mg), and pyridine (40 mg, 0.51 mmol) was added to the
lithiated SBA-15 mixture and stirred at room temperature
inside the glove box (48 h). The metallated Ru-salen SBA-
15 8 was recovered via filtration and washed with copious
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Adv. Synth. Catal. 2009, 351, 1344 – 1354

Recyclable Polymer- and Silica-Supported Ruthenium(II)-Salen Bis-pyridine Catalysts
FULL PAPERS
THF, methanol, DCM, toluene, hexane, and ether. The re-
sulting dark brown solid was dried under high vacuum at
room temperature overnight and stored in the glove box.
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[8] A. Cornejo, J. M. Fraile, J. I. Garcia, E. Garcia-Verdu-
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12107.
All cyclopropanation reactions were carried out inside a ni-
trogen glove box. Prior to reaction, the mass of the empty
flask and stir bar was recorded. Ru-salen catalyst
(0.01 mmol, 0.02 equiv.), DCM (1 mL), and styrene (260 mg,
2.5 mmol, 5 equiv.) were added to the 10-mL pear-shaped
flask. A solution of DCM (2.5 mL), tridecane (92.2 mg, 1
equiv.), and EDA (65 mg, 1 equiv., 88 wt% in DCM by
1H NMR) was added dropwise over a 20-min period to the
catalyst solution to initiate the reaction. Samples (20 mL)
were periodically removed and filtered with acetone (1 mL)
through silica gel and a cotton plug to remove the catalyst.
The samples were analyzed via GC with reference to the tri-
decane internal standard. Upon completion, the reaction
mixture was diluted with THF (3 mL). The catalyst was al-
lowed to settle gravimetrically and the solution was re-
moved via pipette. This procedure was repeated once with
THF and twice more with ethyl ether. For the recycling ex-
periments using the pyridine treatment, pyridine
(10 mLmgÀ1 catalyst, generally 300 mL) was added to each
wash cycle. The catalyst was dried under vacuum and re-
turned to the glove box. All recycle experiments were
scaled to the mass of recovered catalyst due to losses during
each cycle from sampling and washing (typically 13% loss
per cycle).
[10] A. Cornejo, J. M. Fraile, J. I. Garcia, M. J. Gil, S. V.
Luis, V. Martinez-Merino, J. A. Mayoral, C. R. Chim.
2004, 7, 161.
[11] Y. Ferrand, P. Le Maux, G. Simonneaux, Tetrahedron:
Asymmetry 2005, 16, 3829.
[12] J. L. Zhang, Y. L. Liu, C. M. Che, Chem. Commun.
2002, 2906.
[13] S. Syukri, W. Sun, F. E. Kꢄhn, Tetrahedron Lett. 2007,
48, 1613.
[14] C. S. Gill, K. Venkatasubbaiah, N. T. S. Phan, M. Weck,
C. W. Jones, Chem. Eur. J. 2008, 14, 7306.
[15] a) M. Holbach, M. Weck, J. Org. Chem. 2006, 71, 1825;
b) X. L. Zheng, C. W. Jones, M. Weck, Chem. Eur. J.
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[16] X. L. Zheng, C. W. Jones, M. Weck, J. Am. Chem. Soc.
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[17] X. L. Zheng, C. W. Jones, M. Weck, Adv. Synth. Catal.
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[18] S. Jain, X. L. Zheng, C. W. Jones, M. Weck, R. J. Davis,
Acknowledgements
Inorg. Chem. 2007, 46, 8887.
[19] M. Holbach, X. L. Zheng, C. Burd, C. W. Jones, M.
Weck, J. Org. Chem. 2006, 71, 2903.
[20] A. Heckel, D. Seebach, Helv. Chim. Acta 2002, 85, 913.
[21] N. Madhavan, C. W. Jones, M. Weck, Acc. Chem. Res.
2008, 41, 1153.
The authors acknowledge financial support of this work by
the DOE-BES through Catalysis Science contract DE-FG02–
03ER15459. We also thank Dr. Carsten Sievers for assistance
obtaining solid state NMR spectra.
[22] S. Kannan, R. Ramesh, Polyhedron 2006, 25, 3095.
[23] K. N. Kumar, G. Venkatachalam, R. Ramesh, Y. Liu,
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[26] The slight difference in selectivities between 4a and 4b
may possibly be explained by the shorter linker of 4a
compared to 4b. Due to the closer proximity of the po-
lymer backbone to the Ru-salen active site for 4a, in-
creased steric interference may be causing the slight
drop in selectivity. The longer, flexible linker of 4b may
lessen the steric hindrance, thereby producing higher
selectivities.
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